ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3752A>C (p.His1251Pro)

dbSNP: rs1567852526
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001222384 SCV001394481 uncertain significance Neurofibromatosis, type 1 2023-06-20 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 950635). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 24789688). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1251 of the NF1 protein (p.His1251Pro).
GeneDx RCV004812388 SCV005437434 uncertain significance not provided 2024-06-14 criteria provided, single submitter clinical testing Observed in an individual with suspected neurofibromatosis type 1 (PMID: 24789688); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24789688, 25486365, 22807134)

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